Since dosage forms which take into consideration the ease of swallowing by patients are scarce in spite of the existence of various known dosage forms of pharmaceutical preparations for oral administration use, great concern has been directed toward the development of a dosage form which can be easily handled especially by the aged or children who have difficulty in swallowing a solid preparation.
For example, in the case of tablets and capsules frequently used as oral preparations, many aged patients or children having weak swallowing power are unwilling to take these solid preparations complaining that the drug is difficult to swallow or stops in the pharynx or gullet.
In the case of powders and granules, they are difficult to swallow because of their aptness to remain in the buccal cavity and therefore to cause an unpleasant feeling in the mouth. In some cases, the aged will be choked with powders or feel a pain or unpleasantness due to granules lodged between false teeth. In addition, powders and granules have to be used after tearing each package, but the aged or children often have difficulty in tearing the package or spill a portion of its contents.
To take these oral preparations, it is necessary to use water, and the aged or children especially require a large volume of water in many cases because of the swallowing difficulty. However, there is a situation that it is necessary to drink water moderately, especially before retire to bed because of the urination problem at night. In addition, in the case of patients who have to take oral preparations constantly while making daily life, water can hardly be obtained in certain cases depending on circumstances, thus sometimes entailing decline in the compliance.
Syrups and the like are regarded as desirable dosage forms for the aged or children, but the aged or children who have difficulty in measuring the necessary volume cannot be expected to use such preparations in correct dose. In addition, since there are many aged patients who can hardly take liquid preparations by mouth by themselves, such dosage forms cannot always be regarded as suitable dosage forms for the aged and children when trouble at the time of drug-taking is taken into consideration, except for a case in which a patient can ask a nurse for a helping hand.
On the basis of the above, when the forthcoming social condition of advanced age is taken into consideration, development of a dosage form which can be used easily especially by the aged seems to be an immediate need, because the morbidity rate of chronic diseases increases with advance in age and patients of advanced age have a tendency to take drugs for a long period of time. Also, in order to keep the quality of life, it is desirable to develop a dosage form which can be easily swallowed and handled according to the ability and life condition of each patient.
Several pharmaceutical preparations which dissolve or disintegrate in the buccal cavity are known as suitable dosage forms for the aged, children or patients who dislike taking drugs. For example, JP-B-62-50445 discloses a solid preparation having an open matrix network structure which is obtained by freezing an aqueous solution containing gelatin as the main component and a pharmaceutical substance and then sublimating the solvent. (The term "JP-B" as used herein means an "examined Japanese patent publication".) According to this patent publication, the open matrix network structure has a density of 10 to 200 mg/ml and disintegrates rapidly in water within 10 seconds by a tablet disintegration test. It also discloses that spitting of the preparation by patients who dislike drug-taking can be prevented, because the preparation disintegrates rapidly within 1 to 2 seconds in the buccal cavity of the patient and is swallowed together with saliva.
However, because of the rapidly disintegrating property, this open matrix structure has an insufficient strength and is so brittle that its hardness cannot be measured. In consequence, the usual Press Through Pack (blister packaging) and the like from which tablets can be easily taken out cannot be used for this preparation, which therefore requires a specific seal-peeling type packaging, and the preparation is extremely difficult to handle because of its aptness to cause breakage and cracking during its delivery or carrying or when it is taken out from its package at the time of its use. Being sensitive to moisture, it also has a problem of causing stickiness on the surface of the preparation even when it is merely put in the hand. In consequence, this dosage form is not practically appropriate because of its difficulty in handling especially by the aged or children.
JP-A-2-32014 discloses a molded tablet which is produced by temporarily mixing solid components such as sugar, active ingredient and the like with a small volume of a volatile liquid binder sufficient to form a slightly wet lump and putting the thus formed lump into a mold by force to evaporate the liquid binder. (The term "JP-A" as used herein means an "unexamined published Japanese patent application".) However, since this molded tablet is prepared by forced pack molding of a clayey material and drying, air contamination and the like cannot be avoided, thus causing irregularities in the drug content, shape, hardness and the like and entailing inferior practicability. In addition, the production process is not applicable to industrial tablet production, because it requires a special mold packing apparatus.
JP-A-3-56412 discloses an intrabuccally dissolving preparation which is obtained by freeze-drying sugars. However, since this preparation has low hardness, it cannot be applied to conventional Press Through Pack (blister packaging) and has low practicability from the viewpoint of preparation handling. In addition, its production process has low industrial productivity, because the highly viscous suspension to be filled in a mold cannot be applied to the usual liquid filling apparatus, thus requiring a special filling apparatus, and because irregularities in the shape, weight and the like of the final preparation occur.